We propose an integrative training program in translational research in neural injury and neurodegeneration for MDs or MD-PhDs who finish clinical training in Neurology, Neurosurgery, Psychiatry, Ophthalmology, Anesthesia, Emergency Medicine or any other clinical neuroscience specialty, and desire academic careers in laboratory-based translational research in the Neurobiology of Disease. Clinician-scientists have a unique ability to ask new scientific questions inspired by patient observations, and are singularly situated to communicate and collaborate with both PhD scientists and health care providers. The program is built around mentoring relationships in which two experienced faculty trainers guide a trainee's research development. Mentors will be chosen to offer complementary experience to the trainee. Trainees will have access to a minimum of 22 laboratories within the "core" group of Penn faculty, but could train in other laboratories as well. Trainee research must be collaborative, asking questions relevant to at least two groups. The 2-year program will focus on neuroprotection for acute and chronic neurodegenerative diseases and conditions, including stroke;brain and spinal cord injury;Alzheimer's, Parkinson's and motor neuron diseases;epilepsy;retinal degeneration;depression;behavioral disorders;autism. Training will focus heavily on laboratory research, with trainee projects directed toward understanding the genetic, molecular and cellular pathophysiology and the development of strategies for prevention, treatment, or cure. Didactic training will include: coursework in the University's comprehensive Neurobiology of Disease curriculum and workshops in clinical trial methodology, grant preparation, statistics, bioethics, patient-oriented research, and new drug development. The program would begin with 2 trainees, growing to 5 within 2 years. A unique feature of the proposed Program is that prospective trainees will know of their acceptance into the Program well before their clinical training ends. This will allow trainees to plan for this stage of their professional development by taking advantage of the time during residency to gain research, and research-related experience, with the final effect of expanding the total amount of training they will have acquired before writing their K-award proposal. It is expected that trainees who complete this program will be very competitive for independent research grant funding, will become faculty members at academic medical centers, and will pursue careers in translational research in the neurobiology of disease. Relevance: We propose to teach physicians to conduct laboratory research into causes of neurological diseases. A better understanding will lead to the development of new treatments and cures.